The primary goal of the project is the analysis of the expression and regulation of endogenous retroviral sequences. Studies include a survey of the distribution of human retroviral mRNAs, characterization of their structure, analysis of their regulation, and ultimately investigation into potential functions of retroviral sequences in normal and malignant tissues. Subgenomic probes derived from the LTR, gag, pol, and env regions of molecularly cloned human, monkey, and murine endogenous retroviral DNA have been used in Northern blot hybridizations to analyze retroviral mRNA expression in these species. Human endogenous retroviral mRNA has been detected in a wide variety of human tissues: LTR and env hybridizing mRNAs in placenta, colon carcinoma, breast carcinoma and choriocarcinoma cells; gag, pol, and env mRNA in a number of hematopoietic cell lines, including two immature T cell leukemias and frequent "LTR-only" mRNAs in a large number of malignant cell lines as well as normal spleen and appendiceal carcinoma tissue. cDNA clones of human placental retroviral mRNAs have been obtained and a cDNA clone of a 1.7 kb LTR-env mRNA has been found to contain putative gp70 and LTR sequences but is lacking the p15E region. A cDNA clone of a second 3.0 kb placental LTR env mRNA contains putative p15E sequences as well as gp70 and LTR sequences. The structure of aberrantly sized retroviral mRNAs present in normal mouse tissues has been analyzed by Norther blot hybridization. In addition to the expected 8.4 and 3.0 kb retroviral mRNAs, additional species of 7.0, 6.2, 5.8, 3.8, 1.8, and 1.3 kb have been detected and shown to contain variable deletions, particularly of the env region.